Abstract
Introduction
Oral antiviral medications are important tools for preventing severe COVID-19 outcomes. However, their uptake remains low for reasons that are not entirely understood. Our study aimed to assess the association between perceived risk for severe COVID-19 outcomes and oral antiviral use among those who were eligible for treatment based on Centers for Disease Control and Prevention (CDC) guidelines.
Methods
We surveyed 4034 non-institutionalized US adults in April 2023, and report findings from 934 antiviral-eligible participants with at least one confirmed SARS-CoV-2 infection since December 1, 2021 and no current long COVID symptoms. Survey weights were used to yield nationally representative estimates. The primary exposure of interest was whether participants perceived themselves to be “at high risk for severe COVID-19.” The primary outcome was use of a COVID-19 oral antiviral within 5 days of suspected SARS-CoV-2 infection.
Results
Only 18.5% of antiviral-eligible adults considered themselves to be at high risk for severe COVID-19 and 16.8% and 15.9% took oral antivirals at any time or within 5 days of SARS-CoV-2 infection, respectively. In contrast, 79.8% were aware of antiviral treatments for COVID-19. Perceived high-risk status was associated with being more likely to be aware (adjusted prevalence ratio [aPR]: 1.11 [95% confidence interval (CI) 1.03–1.20]), to be prescribed (aPR 1.47 [95% CI 1.08–2.01]), and to take oral antivirals at any time (aPR 1.61 [95% CI 1.16–2.24]) or within 5 days of infection (aPR 1.72 [95% CI 1.23–2.40]).
Conclusions
Despite widespread awareness of the availability of COVID-19 oral antivirals, more than 80% of eligible US adults did not receive them. Our findings suggest that differences between perceived and actual risk for severe COVID-19 (based on current CDC guidelines) may partially explain this low uptake.
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Avoid common mistakes on your manuscript.
Why carry out this study? |
Though oral antiviral medications are important tools to prevent severe COVID-19 outcomes, uptake remains low for reasons that are not entirely understood. |
We investigated the relationship between perceived risk for severe COVID-19 outcomes and use of oral antiviral treatment for COVID-19 among those who were eligible for treatment. |
What was learned from the study? |
Out of 934 non-institutionalized US adults surveyed in April 2023 who were antiviral-eligible with at least one confirmed SARS-CoV-2 infection since December 1, 2021, only 18.5% considered themselves to be at high risk for severe COVID-19 and 15.9% took oral antivirals within 5 days of SARS-CoV-2 infection. |
Perceived high-risk status was associated with being more likely to be aware, to be prescribed, and to take oral antivirals at any time or within 5 days of infection. |
Differences between perceived and actual risk for severe COVID-19 may partially explain low oral antiviral uptake. |
Introduction
In addition to COVID-19 vaccination [1], oral antiviral medications such as nirmatrelvir/ritonavir and molnupiravir are important tools for preventing severe COVID-19 outcomes. These drugs were first approved by the Federal Drug Administration (FDA) for Emergency Use Authorization (EUA) in December 2021 for individuals at high risk for severe COVID-19 disease [2, 3], based on clinical trials in the summer and fall of 2021 showing substantial reductions in hospitalizations and deaths among high-risk, non-hospitalized and unvaccinated adults with SARS-CoV-2 infection [4, 5]. In the Omicron era, real-world effectiveness of nirmatrelvir/ritonavir against COVID-19-related hospitalizations, disease progression, and death has been demonstrated in a number of different outpatient settings, including among individuals with prior SARS-CoV-2 immunity through infection or vaccination, with a high level of protection for those older than 65 or with comorbidities [6,7,8,9,10,11,12,13]. Evidence of molnupiravir effectiveness among high-risk vaccinated adults, however, is mixed [14,15,16,17,45], underscoring the importance of physician recommendation for improving oral antiviral uptake.
Our findings also give some insight into other possible reasons for non-use; we found that among eligible individuals who were not prescribed oral antivirals for their last SARS-CoV-2 infection, more than half did not think they needed it, while a healthcare provider refused a prescription for less than 5% of individuals. Using data from three rounds of the US Census Household Pulse Survey collected between June and August 2022, an analysis of reasons for not receiving oral antiviral treatment among individuals 65 or older with at least mild symptoms cited not feeling very sick (20.6%) and not thinking they needed treatment (16.4%) as the most common reasons for not taking oral antivirals, followed by not having the treatment offered or recommended to them by a healthcare provider (14.5%) [46]. The same study also found that not seeing oneself as a member of a high-risk group was a fairly uncommon reason cited for not taking oral antivirals (4.9%). This is surprising, given our finding that the majority of antiviral-eligible individuals do not perceive themselves to be at high risk for severe COVID-19 outcomes.
Though the survey design used in this study used sampling and weighting methods to reduce any bias resulting from sociodemographic differences in recruitment and response rates and has been shown to provide reliable and nationally representative estimates for other COVID indicators [33], we were unable to account for potential nonresponse bias related to SARS-CoV-2 infection history or oral antiviral use. For example, if people who used oral antivirals were more likely to complete the survey, estimates may be inflated. However, our approach benefits from the ability to reflect perceived risk, COVID-19 outcomes, antiviral eligibility, and oral antiviral use among those who may not have accessed the healthcare system when they last had COVID-19.
Our study has several other limitations worth noting. Data were self-reported, and there is the potential for misclassification and reporting bias. However, studies comparing self-reported COVID-19 vaccine status with electronic health records or vaccine registries have found more than 90% agreement between the two [47,48,49]. Further, self-reported health conditions [50] and use of medication [51] have been found to have high specificity and moderate sensitivity; thus, we may have underestimated the prevalence of health conditions or oral antiviral use. Relatedly, our estimates of SARS-CoV-2 infection timing and oral antiviral use were likely more accurate for more recent infections. In addition, because our definition of SARS-CoV-2 infection was based on self-reported diagnosis by a health care provider or testing, we would have missed asymptomatic infections and symptomatic infections among those who did not receive a COVID test or seek care (i.e., possible infections), leading to an underestimated prevalence of those with a history of SARS-CoV-2 infection. In our sample, none of those with possible infections reported antiviral prescription. This group requires further investigation, however, because they may have barriers to knowledge, access to testing, and access to care that could get in the way of antiviral use.
The cross-sectional nature of this study made it impossible to determine the temporality of responses, since risk and outcomes were assessed at the same time. While one might predict an individual’s perceived risk to influence their decisions around treatment once sick, one might also predict that experience with an illness might influence that individual’s perception of their risk going forward (e.g., if their symptoms were very mild). We did not ask about the severity or nature of symptoms experienced by individuals at the time of their last SARS-CoV-2 infection, which might be important factors to investigate further to better understand what influences an individual to seek antiviral treatment. In addition, participants were given only two possible reasons for non-use of oral antivirals, which limited our ability to better understand non-use. We plan to conduct a more granular evaluation of barriers to oral antiviral use, including elements of both patient and provider decision-making following the transition of nirmatrelvir/ritonavir and molnupiravir to the commercial market in November 2023 in the United States [52].
Conclusions
In conclusion, we found that less than 20% of antiviral-eligible adults (based on CDC criteria for high risk) perceived themselves to be at high risk for severe COVID-19 outcomes. This misperception of risk status, and thus antiviral eligibility, may be a contributor to suboptimal COVID-19 oral antiviral uptake to date, despite broad awareness of COVID-19 treatment options. Our findings suggest the need for additional strategies to ensure that individuals better under their COVID-19 risk, which may improve uptake of available treatment options.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors wish to acknowledge the survey participants and Ipsos for completing survey
sampling and data collection.
Funding
This study was conducted as a collaboration between City University of New York (CUNY) and Pfizer. CUNY is the study sponsor. Pfizer, Inc. had no role in the collection, management, or analysis of the data; or the decision to submit the manuscript for publication. The journal’s Rapid Service Fee was funded by the authors.
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Kate Penrose contributed to the conceptualization and design of the analysis, conducted the statistical analysis, and drafted the original manuscript. Avantika Srivastava, Yanhan Shen, McKaylee M. Robertson, Sarah G. Kulkarni, Kristen E. Allen, Thomas M. Porter, Laura Puzniak, John M. McLaughlin, and Denis Nash contributed to the design of the analysis, interpretation of results, and reviewing and editing of the manuscript.
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Conflict of Interest
Kristen E. Allen, Thomas M. Porter, Laura Puzniak and John M. McLaughlin are employees of Pfizer Inc. and hold stock and/or stock options of Pfizer Inc. Denis Nash discloses consulting fees from AbbVie and Gilead, and a research grant from Pfizer paid to his institution. Kate Penrose, Avantika Srivastava, Yanhan Shen, McKaylee M. Robertson, and Sarah G. Kulkarni report support from Pfizer through a research grant paid to their institution.
Ethical Approval
The study protocol was approved by the Institutional Review Board at the City University of New York (CUNY IRB 2022-0407). The Institutional Review Board determined that the study met the criteria for Human Subject Research Exemption based on collection of de-identified survey data only. Consent to receive survey invitations from the Ipsos KnowledgePanel is obtained during the recruitment process. Before responding to a survey, individuals are reminded that their responses will be used for research purposes only and that they can choose not to participate or answer any question.
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Penrose, K., Srivastava, A., Shen, Y. et al. Perceived Risk for Severe COVID-19 and Oral Antiviral Use Among Antiviral-Eligible US Adults. Infect Dis Ther (2024). https://doi.org/10.1007/s40121-024-01003-3
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DOI: https://doi.org/10.1007/s40121-024-01003-3